Our working hypothesis is that the Sudden Infant Death Syndrome is due to a failure of the respiratory control system. We are studying this system in two areas, neural and chemical control. Our investigations in neural control demonstrate that premature infants demonstrate active pulmonary stretch receptor reflex activity. They show a marked dependence on afferent lung volume information to maintain respiratory rate and to achieve load compensation while full term infants, like adult man, do not. We have demonstrated a significant difference in the strength of the vagally mediated inflation reflex during intra and extra-uterine development and the loss of the reflex is delayed in prematurely born infants. Chemical control of ventilation studies has shown an apparent increase in response to CO2 with gestational age. It is difficult to interpret these studies with the marked increase in lung volume growth with gestational and conceptual age. We have been studying CO2 response in newborn infants using an occlusion technique during CO2 rebreathing. The changes observed may represent declining vagal inflation reflex input or increasing sensitivity of central chemoreceptors. The response may also be influenced by altering properties of the mechanics of the chest wall.